The chemical and molecular analysis of the surface and thin surface layers of solid materials is usually based on the energetic stimulation of the sample surface and the mass spectrometry analysis of fragments ejected from the surface. There are two commonly used types of instruments used for this type of analysis.
The first of the two common types of instruments is based on the use of “primary” ion beams to excite the sample and to eject charged atomic and molecular species (referred to as “secondary” ions) that are analyzed by a mass spectrometer. This type of instrumental technique is normally called Secondary Ion Mass Spectrometry (SIMS). The SIMS instrument may also have an additional mode of ionizing neutral fragments that are emitted at the same time as the secondary ions and this mode of operation is normally called Post Ionization SIMS. To obtain the highest collection efficiency, sensitivity, and separation of the different species based on the mass-to-charge (m/z) ratio of these species, a Time-of-Flight (TOF) mass spectrometer may be used in this SIMS instrument. The technique is therefore commonly referred to as TOF-SIMS. The TOF-SIMS instrument may be used in various other operating modes. For example, with the use of a scanned, micro-focused primary ion beam, mass resolved images of the sample can also be obtained with the TOF-SIMS instrument; this is generally known as the microprobe mode of operation. Further, a microscope mode of operation of the TOF mass spectrometer can also be used to obtain mass resolved images of the sample with the TOF-SIMS instrument. Exemplary embodiments thereof, for example, are described in U.S. Pat. No. 5,128,543, herein incorporated by reference.
The second type of instrument uses a photon source to excite the sample material to cause the ejection of fragments from the surface. The analysis of the fragments emitted as charged particles (i.e., ions) from the surface by a mass spectrometer is commonly known as Laser Desorption Mass Spectrometry. To increase the efficiency of the emission of charged particles (i.e., ions), specially selected organic matrix materials can be added to the surface of the sample. This refinement is commonly known as Matrix Assisted Laser Desorption Ionization (MALDI). To obtain the highest collection efficiency, sensitivity and separation of the different emitted species based on the mass-to-charge ratio, a Time-of-Flight mass spectrometer is normally used in this MALDI instrument although other types of mass spectrometers have also been used in MALDI instruments. With the use of a scanning stage and a micro-focused laser photon source, mass resolved images of the sample can also be obtained with MALDI; this is generally known as the microprobe mode of operation. A microscope mode of operation of the TOF mass spectrometer can also be used to obtain mass resolved images of the sample with MALDI analysis. Exemplary embodiments thereof, for example, are described in the article, S. L. Luxembourg, et al., “High Spatial Resolution Mass Spectrometric Imaging of Peptide and Protein Distributions on a Surface Imaging Mass Spectrometry”, Anal. Chem. 2004 76(18) 5339-5344 as well as in the article, L. A. McDonnell et al., “Imaging Mass Spectrometry”, Mass Spectrometry Reviews, 2007, 26, 606-643, both herein incorporated by reference.
The unique identification of the charged species emitted with either the TOF-SIMS or the MALDI techniques was historically based on the high mass resolution and mass accuracy of the TOF mass spectrometer. However, for mass-to-charge species (m/z species) with a mass above approximately 500 dalton (Da), the mass resolution and mass accuracy of the TOF mass spectrometer may not provide a unique molecular fragment identification of the emitted species. Historically, for the mass spectrometry analysis of higher mass liquid and gas phase molecules, a technique of Mass Spectrometry/Mass Spectrometry (MS/MS) has been used to provide a unique molecular fragment identification of many high mass species. This technique is based on the selection of a high mass ion in a first stage mass spectrometer (referred to as a “precursor” ion), followed by an energetic activation resulting in fragmentation of the precursor ion, followed by a second mass spectrometry analysis of the resulting fragment ions. Exemplary embodiments thereof, for example, are described by Boesl et al. in U.S. Pat. No. 5,032,722, herein incorporated by reference. The use of MALDI MS/MS is discussed in Andersson, et al., “Imaging Mass Spectrometry of Proteins and Peptides: 3D Volume Reconstruction”, Nature Methods 2008 5, 101-108 as well as L. A. McDonnell et al, “Imaging Mass Spectrometry”, Mass Spectrometry Reviews 2007, 26, 606-643, both herein incorporated by reference.
Exemplary methods and apparatus to obtain MS/MS data with the mass spectrometry spectral data containing both the precursor ion data and the fragment ion data, along with exemplary embodiments thereof, are described by Alderdice, et al. in U.S. Pat. No. 5,206,508, herein incorporated by reference. The apparatus described in U.S. Pat. No. 5,206,508 provides a tandem mass spectrometry system, capable of obtaining tandem mass spectra for each parent ion without separate spectra of precursor ions of differing mass from fragment ions of different mass. The data shown in FIG. 4 of U.S. Pat. No. 5,206,508 illustrate the overlap in the spectral display of the precursor ions and the fragment ions. This spectral overlap of precursor and fragment ions is a result of the single detector after the second mass analyzer. The overlapping of the data in the spectra makes this method and apparatus unworkable for polymer and biological samples that are typical for imaging MALDI and imaging TOF-SIMS analyses.
There are, for example, three apparatus concepts that may provide imaging TOF-SIMS data with MS/MS data based on a sequential mode of operation (e.g., imaging precursor ion mass spectrometry analysis followed by fragment ion mass spectrometry analysis). These three apparatus concepts require that a choice be made between the acquisition of secondary ion (e.g., precursor ion) mass spectrometry data or fragment ion mass spectrometry data. This defines the sequential nature of the instrument operation in such apparatus concepts. This sequential mode of operation prevents analytical TOF-SIMS data and MS/MS data from being acquired from the same analytical sample volume.
The first apparatus concept is based on a reflectron analyzer which allows the rejection of the precursor ions before the ion mirror and allows the fragment ions that result from precursor ion uni-molecular ion decay in the flight path between the sample and the reflectron to be mass analyzed (see, e.g., D. Touboul, et al., Rapid Commun. Mass Spectrom. 2006; 20: 703-709, herein incorporated by reference). This apparatus concept depends on the creation of fragment ions by the in-flight decay of metastable ions and is referred to as post-source decay (PSD). This described apparatus concept does not include an activation device between the reflectron used for precursor ion TOF-SIMS and a second mass spectrometer for acquisition of a MS/MS fragment ion spectra.
The second apparatus concept is a hybrid triple quadrupole TOF mass spectrometer equipped with an ion gun to produce TOF-SIMS ions. The apparatus concept uses a series of three quadrupole mass spectrometers followed by an orthogonal TOF mass spectrometer to acquire precursor ion TOP-SIMS data. In a second mode of operation, the second quadrupole mass spectrometer may also be used to select a precursor ion from the TOF-SIMS imaging experiment. The third quadrupole can then be operated at high gas pressure (e.g., in an activation cell) to produce fragment ions that can be measured in the orthogonal TOF mass spectrometer (see, e.g., A. Carado, et al., Appl. Surf. Sci. 2008; 255: 1610-1613, herein incorporated by reference). This described apparatus concept does not simultaneously and in parallel measure the precursor ion TOF-SIMS imaging data and the fragment ion MS/MS data.
The third apparatus concept is a reflectron analyzer with an integral gas collision cell in the reflectron flight path. This apparatus concept requires a choice between the acquisition of the precursor ions for imaging TOF-SIMS or the use of a high pressure gas in the collision cell to activate the precursor ions to produce fragment ions which can be mass analyzed in the rest of the reflectron flight path (see, J. S. Fletcher, et al., Anal. Chem. 2008; 80 9058-9064, herein incorporated by reference). This product concept cannot simultaneously and in parallel measure the precursor ion TOF-SIMS imaging data and the fragment ion MS/MS data.